1. Field of the Invention
The present invention relates to methods of delivery of pharmaceuticals or drug candidates and, more specifically, to the use of ammonia to neutralize a low pH aerosol.
2. Description of the Related Art
Many active pharmaceutical ingredients (“APIs”) or drug candidates (“DCs”) have poor aqueous solubility. The solubility of the API or DC can be pH-dependent, and often the API or DC can only be dissolved in a low pH solution. The solubility can further depend on the particular acid used to lower the pH. For example, an API or DC may exhibit better solubility in p-toluene sulfonic acid compared to methanesulfonic acid or phosphoric acid. Other acids that are used to dissolve an API or DC include sulfuric acid and hydrochloric acid, among others.
Some APIs or DCs are designed to be delivered by inhalation as a treatment for a disease of the lung or to be absorbed through the lung to treat a systemic disease, among other uses. However, to deliver an API or DC by inhalation it first must be aerosolized. Aerosols can contain particles of various sizes, which may be varied in order to control delivery of the API to different parts and/or levels of the lung. Particle sizes can range from less than 100 nm to more than 5 microns.
There are many ways to aerosolize a compound. One such method is to aerosolize a liquid containing the API or DC dissolved in a solution. Devices that aerosolize liquid include jet nebulizers that use compressed air, such as the PARI nebulizer or the Medi-Nuclear nebulizer. Other devices use ultrasound to generate an aerosol. Still other devices use mechanical vibration or piezoelectric energy.
An API or DC dissolved in a low pH solution and aerosolized for delivery can cause inflammation and injury to the airways and lung if inhaled. Accordingly, there is a continued need to increase the pH of a low pH aerosol prior to inhalation.